Renin-angiotensin System Genes Research Articles

Angiotensin-(1-7) Improves Integrated Cardiometabolic Function in Aged Mice.

Angiotensin (Ang)-(1-7) is a beneficial renin–angiotensin system (RAS) hormone that elicits protective cardiometabolic effects in young animal models of hypertension, obesity, and metabolic syndrome. The impact of Ang-(1-7) on cardiovascular and metabolic outcomes during aging, however, remains unexplored. This study tested the hypothesis that Ang-(1-7) attenuates age-related elevations in blood pressure and insulin resistance in mice. Young adult (two-month-old) and aged (16-month-old) male C57BL/6J mice received Ang-(1-7) (400 ng/kg/min) or saline for six-weeks via a subcutaneous osmotic mini-pump. Arterial blood pressure and metabolic function indices (body composition, insulin sensitivity, and glucose tolerance) were measured at the end of treatment. Adipose and cardiac tissue masses and cardiac RAS, sympathetic and inflammatory marker gene expression were also measured. We found that chronic Ang-(1-7) treatment decreased systolic and mean blood pressure, with a similar trend for diastolic blood pressure. Ang-(1-7) also improved insulin sensitivity in aged mice to levels in young mice, without effects on glucose tolerance or body composition. The blood pressure–lowering effects of Ang-(1-7) in aged mice were associated with reduced sympathetic outflow to the heart. These findings suggest Ang-(1-7) may provide a novel pharmacological target to improve age-related cardiometabolic risk.

Activation of the renin-angiotensin system in high fructose-induced metabolic syndrome.

High fructose intake induces hyperglycemia and hypertension. However, the mechanism by which fructose induces metabolic syndrome is largely unknown. We hypothesized that high fructose intake induces activation of the renin-angiotensin system (RAS), resulting in hypertension and metabolic syndrome. We provided 11-week-old Sprague–Dawley rats with drinking water, with or without 20% fructose, for two weeks. We measured serum renin, angiotensin II (Ang II), and aldosterone (Aldo) using ELISA kits. The expression of RAS genes was determined by quantitative reverse transcription polymerase chain reaction. High fructose intake increased body weight and water retention, regardless of food intake or urine volume. After two weeks, fructose intake induced glucose intolerance and hypertension. High fructose intake increased serum renin, Ang II, triglyceride, and cholesterol levels, but not Aldo levels. High fructose intake increased the expression of angiotensinogen in the liver; angiotensin-converting enzyme in the lungs; and renin, angiotensin II type 1a receptor (AT1aR), and angiotensin II type 1b receptor (AT1bR) in the kidneys. However, expression of AT1aR and AT1bR in the adrenal glands did not increase in rats given fructose. Taken together, these results indicate that high fructose intake induces activation of RAS, resulting in hypertension and metabolic syndrome.

Training-Induced Deactivation of the AT1 Receptor Pathway Drives Autonomic Control and Heart Remodeling During the Transition From the Pre- to Hypertensive Phase in Spontaneously Hypertensive Rats.

The effects of hypertension and exercise training (T) on the sequential interplay between renin-angiotensin system (RAS), autonomic control and heart remodeling during the development of hypertension in spontaneously hypertensive rats (SHR), was evaluated.Methods and Results:Time course changes of these parameters were recorded in 4-week-old SHR submitted to a T or sedentary (S) protocol. Wistar Kyoto rats served as controls. Hemodynamic recordings were obtained in conscious rats at experimental weeks 0, 1, 2, 4, and 8. The left ventricle (LV) was collected to evaluate RAS gene and protein expression, cardiomyocytes' hypertrophy and collagen accumulation. Pre-hypertensive SHR exhibited augmented AT1R gene expression; at 5 weeks, they presented with elevated pressure, increased LV angiotensinogen and ACE mRNA expression, followed by sympathoexcitation (from the 8thweek onwards). Marked AT1R protein content, myocytes's hypertrophy, collagen deposition and increased pressure variability were observed in 12-week-old sedentary SHR. In addition to attenuating all these effects, T activated Mas receptor expression augmented parasympathetic modulation of the heart, and delayed the onset and reduced the magnitude, but did not block the development of genetic hypertension. The close temporal relationship between changes in the LV ACE-Ang II-AT1R axis, autonomic control and cardiac remodeling at both the establishment of hypertension and during exercise training reveals the essential role played by the AT1R pathway in driving cardiac remodeling and autonomic modulation during the transition from the pre- to hypertensive phase.

Maternal high-fructose intake induces hypertension through activating histone codes on the (pro)renin receptor promoter

High-fructose intake induces hypertension via the renal expression of (pro)renin receptor (PRR) that stimulates the expression of sodium/hydrogen exchanger 3, Na/K/2Cl cotransporter 2, and genes of the intrarenal renin-angiotensin system. We hypothesize that maternal high-fructose intake induces hypertension in subsequent generation offspring through activating histone codes on the PRR promoter.Mice dams were offered 20% fructose solution during pregnancy and lactation, while the subsequent 1st to 4th generation offspring were raised without fructose. Blood pressure was measured via tail-cuff method. The mRNA and protein expression were determined using quantitative real-time polymerase chain reaction and western blotting, respectively. Histone modification was evaluated using a chromatin immunoprecipitation assay.Maternal high-fructose intake statistically significantly increased blood pressure in the 1st and 2nd generations of offspring compared to the control group. Expression levels of sodium transporters and PRR were increased in the kidneys of the 1st to 3rd generation offspring. Increased enrichment of active histone codes such as H3Ac and H3K4me2 but decreased enrichment of repressive histone codes such as H3K9me3 and H3K27me3 on the PRR promoter were observed in the 1st to 3rd not the 4th generation. Moreover, there was increased the mRNA expression for histone acetyltransferase and methyl transferases for H3K4 in the 1st and 2nd generation offspring compared to the control group.This study implicates that maternal high-fructose intake induces hypertension in multigenerational offspring through activating histone codes on the PRR promoter.

Hypertension in elderly: A study of hypertension in epigenetic perspective

Background: as is known, epigenetic events are defined as modifications in phenotype or gene expression, which caused by interactions between genes and the environment without changing the order of their nitrogenous bases. This article will discuss the role of epigenetics in one of the degenerative diseases that are often found in the elderly, namely hypertension. In this review article, we will mainly discuss the events of histone modification and DNA methylation, for example, DNA methylation in the CpG islands and the acetylation of histone pathway are identified to limit the development of nephrons, thus opening up to lhypertension-related with exposure to high salt diets. Results: lack of maternal water and protein deficiency have been shown to increase the appearance of the renin-angiotensin system gene in the children. Conclusion: these results indicate targets for the interaction of environmental genes in various conditions of hypertension and essential hypertension.

In vitro analysis of the renin-angiotensin system and inflammatory gene transcripts in human bronchial epithelial cells after infection with severe acute respiratory syndrome coronavirus.

Introduction:Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a recently identified coronavirus family member that triggers a respiratory disease similar to severe acute respiratory syndrome coronavirus (SARS-CoV). SARS-CoV and SARS-CoV-2 are very similar to each other in many respects, such as structure, genetics, and pathobiology. We hypothesized that coronaviruses could affect pulmonary tissues via integration with the critical immune genes after their interaction with renin–angiotensin system (RAS) elements. The aim of the present bioinformatics study was to assess expression changes of the RAS and non-RAS genes, particularly immune response genes, in the lung epithelial cells after infection with SARS-CoV.Methods:Linear regression, hierarchical clustering, pathway analysis, and network analysis were performed using the E-GEOD-17400 data set.Results:The whole-genome expression data of the lung epithelial cells infected with SARS-CoV for 12, 24, and 48 hours were analyzed, and a total of 15 RAS family and 29 immune genes were found to be highly correlated with the exposure time to the virus in the studied groups.Conclusion:RAS genes are important at the initiation of the infections caused by coronavirus family members and may have a strong relationship with the exchange of immune genes in due course following the infection.

Perinatal Epigenetic Modulation of the Brain Renin Angiotensin System Programs Cardiometabolic Diseases

Cardiometabolic Disease (CMD) is one of the major health conditions associated with high morbidity and mortality. It is known for disturbed glycemic levels, elevated blood pressure and dyslipidemia. Epigenetic mechanisms especially DNA methylation have recently been shown to exert an essential role in the development of CMD. DNA methyltransferase (DNMT) and Ten eleven translocation (TET) are crucial enzymes controlling DNA methylation and demethylation. Pre‐autonomic neurons in the paraventricular nucleus of the hypothalamus (PVN) act as key regulators for blood pressure (BP) control. We recently reported that the renin‐angiotensin system (RAS) is an important modulator of those neurons via activation of A Disintegrin and Metalloprotease 17 (ADAM17) and Angiotensin II Type 1 receptors (AT1R) contributing to BP dysregulation. We propose that consumption of a hypercaloric diet during pregnancy leads to epigenetic modifications in the progeny’s brain, promoting autonomic dysfunction and hypersensitivity to neurogenic hypertension and metabolic disorders. In this study, C57BL6/J dams were fed a high‐fat high‐sucrose diet (HFHSD) or regular diet (RD) and mated with RD males. After weaning, offspring were put on RD for 3 months and underwent 24 h BP recording (telemetry), pharmacological assessment of autonomic function, blood glucose measurement and a glucose tolerance test before being sacrificed. RNA was extracted from the hypothalamus of HFHSD‐exposed (OH) and RD‐exposed (OR) offspring. mRNA expression for DNMT1, DNMT3a, DNMT3b, Tet1, Tet2, Tet3, AT1R and ADAM17 was quantified using real‐time PCR. Baseline BP recording showed a significant (p<0.05) and sex‐specific increase in systolic BP (140 ±2 vs. 132 ±3 mmHg) and heart rate (654 ±10 vs. 590 ±10 bpm) in OH males compared to OR controls during the active phase (6PM‐6AM). This group also exhibited significantly higher blood glucose levels (168 ±7 vs. 143 ±7 mg/dL) and sympathetic drive to the heart (Bradycardia to propranolol: −152 ±10 vs. −44 ±8 bpm). DNMT3b, Tet2, and Tet3 expression were significantly downregulated in OH mice (unpaired t‐test, p<0.05) while expression of ADAM17 and AT1R, components of the RAS, were upregulated (p=0.002 and 0.005, respectively). To elucidate the mechanisms involved in future experiments, an in vitro model was developed using N2A cells treated with a glucose‐lipid mixture and validated by the significant downregulation of gene expression for DNMT1, DNMT3a (p<0.01), Tet1, Tet3 (p<0.05) in comparison to untreated N2A cells. We conclude that consumption of HFHSD during pregnancy promotes changes in methylation profiles within the hypothalamus, leading to altered gene expression, notably of RAS genes in the brain, which in turn could trigger autonomic dysfunction and hypersensitivity to cardiometabolic disease.Support or Funding InformationAmerican Diabetes Association (1‐19‐IBS‐291), Veterans Affairs Merit Award (BX004294), National Institutes of Health (HL093178 and COBRE P30GM106392), and LSUHSC‐NO Research Enhancement Program.

Anhydramnios, but prenatally normal kidneys: renal tubular dysgenesis – patient with mutations in the renin-angiotensin system gene AGTR1

Abstract Background Prenatally detected oligo- or even anhydramnios may – beside other reasons – be indicative for a diminished or absent urine production. The resulting clinical picture is a “Potter sequence” with arthrogrypotic joint contractions, a flat face and most importantly pulmonary hypoplasia. In severe cases this pulmonary hypoplasia can be life-limiting irrespective of the underlying lesion. Case presentation Our patient initially presented with anhydramnios and normal kidneys at external ultrasonography after 31 weeks of pregnancy. Following spontaneous birth after 37 weeks of gestation, the baby boy was born with all the clinical signs of a “Potter-sequence” along with a severe pulmonary hypoplasia leading to insufficient oxygenation and ventilation. Despite all measures taken, the child died after 8 h of life. Beside life-limiting pulmonary hypoplasia postmortem examination again confirmed macroscopically normal kidneys, but microscopy showed compact and variable sized glomeruli, numerically reduced and immature tubules, a structurally altered renal vascular bed and an expanded medullar interstitium. Immunohistochemical studies revealed the absence of proximal convoluted tubules, shortened proximal straight tubules beside an immaturity and dysmorphogenesis of the other segments of the nephron, and thus proved renal tubular dysgenesis (RTD) as the underlying disease. A homozygous mutation c.377G>C (p.Arg126Pro) in exon 2 of the AGTR1 gene was found, leading to the exchange of a highly conserved arginine to proline. This mutation has not been reported in public databases so far. As expected, both consanguineous parents were heterozygous for this mutation. Conclusion RTD has to be considered in an anuric fetus with apparently normal renal sonography in order to allow adequate prenatal counseling and – if indicated – palliative postnatal care.

The Renin-Angiotensin System in the Central Nervous System and Its Role in Blood Pressure Regulation.

Purpose of the ReviewThe main goal of this article is to discuss how the development of state-of-the-art technology has made it possible to address fundamental questions related to how the renin-angiotensin system (RAS) operates within the brain from the neurophysiological and molecular perspective.Recent FindingsThe existence of the brain RAS remains surprisingly controversial. New sensitive in situ hybridization techniques and novel transgenic animals expressing reporter genes have provided pivotal information of the expression of RAS genes within the brain. We discuss studies using genetically engineered animals combined with targeted viral microinjections to study molecular mechanisms implicated in the regulation of the brain RAS. We also discuss novel drugs targeting the brain RAS that have shown promising results in clinical studies and trials.SummaryOver the last 50 years, several new physiological roles of the brain RAS have been identified. In the coming years, efforts to incorporate cutting-edge technologies such as optogenetics, chemogenetics, and single-cell RNA sequencing will lead to dramatic advances in our full understanding of how the brain RAS operates at molecular and neurophysiological levels.

The role of the renin-angiotensin system gene polymorphisms in the development of carbohydrate disorders in patients with arterial hypertension

Arterial hypertension and type 2 diabetes mellitus are the most widespread comorbid pathologies. The coexistence of these disorders accelerates the development of micro- and macrovascular complications, considerably increases the cardiovascular risk, as well as the risk of stroke and end stage renal disease. The synergism of these two pathologies is caused by the unity of pathogenetic mechanisms. Genetic predisposition also contributes to the development of both pathologies. It is well known that blockade of the renin-angiotensin system slows down the development of type 2 diabetes mellitus and also reduces the frequency of cardiovascular or kidney events in patients with these disorders. Gene polymorphisms of the reninangiotensin system are thoughtfully studied in the context of cardiovascular disease development. Currently, the role of gene polymorphisms in the development of carbohydrate disorders is not established, however, there is a high probability of their influence and importance. The purpose of review is to analyze the accumulated data on the effects of the renin-angiotensin system gene polymorphisms on the development of arterial hypertension and type 2 diabetes mellitus.

Renin–angiotensin system gene polymorphisms and colorectal cancer risk: a meta-analysis

Objective:The renin–angiotensin system gene has been implicated in the progression of colorectal cancer. Nevertheless, the details of that role remain controversial. We performed a meta-analysis to investigate the correlation between renin–angiotensin system gene polymorphisms and colorectal cancer.Methods:We retrieved relevant studies from PubMed and Embase. Subsequently, fixed or random-effects models were used to calculate pooled odds ratios (ORs) with 95% confidence intervals (CIs).Results:We identified six studies of the angiotensin-converting enzyme insertion/deletion (I/D) polymorphism, and two studies of the angiotensinogen M235T polymorphism. The angiotensin-converting enzyme I/D polymorphism did not significantly correlate with colorectal cancer risk in the total population (DD vs. II: OR 0.77, 95% CI 0.39–1.50; DI vs. II: OR 1.05, 95% CI 0.85–1.30; dominant model: OR 0.94, 95% CI 0.68–1.31; recessive model: OR 1.01, 95% CI 0.80–1.27). Similarly, the angiotensinogen M235T polymorphism was not associated with colorectal cancer risk (TT vs. MM: OR 1.38, 95% CI 0.52–3.67; TM vs. MM: OR 1.19, 95% CI 0.96–1.47; dominant model: OR 1.28, 95% CI 0.77–2.14; recessive model: OR 1.17, 95% CI 0.53–2.59).Conclusion:Our findings suggest that the angiotensin-converting enzyme I/D and angiotensinogen M235T polymorphisms are unlikely to correlate with colorectal cancer.

Renin-angiotensin system gene variants and risk of early- and late-onset preeclampsia: A single center case-control study.

Changes in the renin-angiotensin-aldosterone system's (RAAS) activity due to different genetic variations could represent risk factors for the onset of preeclampsia. To test and quantify the relationships of 8 RAAS gene polymorphisms (angiotensinogen (AGT)-M235T, AGT-T174M, angiotensin converting enzyme (ACE)-I/D, ACE8-A2350G, angiotensin II type 1 receptor (AGTR1)-A1166C, angiotensin II type 2 receptor (AGTR2)-C3123A, renin (REN)-G83A, aldosterone synthase (CYP11B2)-T344C) with susceptibility to early- (EOPE) and late-onset preeclampsia (LOPE). We performed polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP) analysis in 217 pregnant women, of whom 87 pregnant women with EOPE/LOPE and 130 normal pregnant women. The relationship between the studied RASS gene polymorphisms and EOPE/LOPE was tested by multiple logistic regressions. The multivariate logistic regression analysis showed that AGT-M235T (adjusted OR = 4.63), AGT-T174M (adjusted OR = 4.13), REN-G83A (adjusted OR = 3) and CYP11B2-C344T (adjusted OR = 3.13) gene polymorphisms remained independent risk factors for EOPE. Moreover, ACE-I/D (adjusted OR = 4.04), ACE-A2350G (adjusted OR = 3.5), AGTR1-A1166C (adjusted OR = 2.73), and REN-G83A (adjusted OR = 2.67) polymorphisms remained independent risk factors for LOPE. The frequency of overweight was significantly different (p = 0.001) in pregnant women with EOPE, LOPE and the control group (LOPE:16, 29.6% vs. EOPE:12, 36.4% vs. control group:16, 12.3%). Pregnant women with EOPE had babies with a significantly lower mean birth weight (2067.9 ± 887.9) in comparison to women with LOPE (mean ± SD: 2860.1 ± 771.1, p < 0.001) and women with normal pregnancies, respectively (mean ± SD: 3324.9 ± 484.9, p < 0.001). We confirmed the influence of the renin-angiotensin-aldosterone system through these 8 genetic variations on the onset of preeclampsia.

Imbalance of the renin–angiotensin system may contribute to inflammation and fibrosis in IBD: novel therapeutic target?

ObjectiveWe evaluated the influence of the renin–angiotensin system (RAS) on intestinal inflammation and fibrosis.DesignCultured human colonic myofibroblast proliferation and collagen secretion were assessed following treatment with angiotensin (Ang) II and...

Distribution of Polymorphisms of the Renin-Angiotensin System Genes (ACE, AGT, and AGTR1), ITGB3, and FTO in Pregnant Patients with Hypertensive Disorders.

The study included pregnant women aged 23-41 years with preeclampsia and gestation-associated arterial hypertension at weeks 27-40 and patients with essential arterial hypertension developing under conditions of the metabolic syndrome and without it. Frequency analysis of polymorphisms of the renin-angiotensin system genes (ACE, AGT, and AGTR1), ITGB3, FTO and their associations confirmed the syndrome nature of hypertensive disorders in pregnancy. The presence allele T of AGT gene and/or allele C of AGTR1 gene in the genotype of patients with preeclampsia was associated with higher BP and pressure load over 24 h. Allele D of ACE gene was also essential for BP parameters (pressure load) in patients with preeclampsia and gestation-associated arterial hypertension. Due to high genetic heterogeneity of the preeclampsia syndrome and genetic differences in the incidence of the studied gene polymorphisms in preeclampsia and gestation-associated arterial hypertension, no direct associations between these gestation disorders and polymorphic markers of the renin-angiotensin system genes can be established. However, polymorphisms of the renin-angiotensin system genes are essential for the 24-h dynamics of BP and pressure load under conditions of hypertensive disorders in pregnancy.

Effects of Angiotensin Converting Enzyme Polymorphism in Acute Myocardial Infarction

It has been established that renin angiotensin system gene polymorphism, such as angiotensin converting enzyme (ACE), could contribute to a higher occurrence of acute myocardial infarction (AMI). Thus, the objective of this study was to evaluate the effects of the variation of the number of copies of the ACE gene in the AMI. Adult mice, genetically modified to express different concentrations of the ACE were used (one, two and three copies – ACE 1, ACE 2 and ACE 3). The animals were divided into 9 groups (n = 10): 3 without AMI ‐ ACE 1, ACE 2 and ACE 3; 3 infarcted groups assessed 7 days after AMI ‐ ACE 1‐MI7, ACE 2‐MI7 and ACE 3‐MI7; 3 infarcted groups assessed 28 days after AMI ‐ ACE 1‐MI28, ACE 2‐MI28 and ACE 3‐MI28. Infarcted animals were submitted to AMI by ligature of the left coronary artery. Cardiac function by echocardiography, heart rate variability (HRV) and baroreflex sensitivity were evaluated. Regarding the echocardiographic data, the E/A ratio was higher in the ACE group 3‐MI7 than in the non‐infarcted groups with one and two copies of ACE and higher than in the infarcted group with two copies of the ACE gene (ACE 3‐MI7: 3.47 ± 0.50 vs. ACE 1: 1.08 ± 0.14, ACE 2: 1.24 ± 0.16 and ACE 2‐MI7: 1.74 ± 0.25); the fractional area change was lower in the infarcted groups ACE 1‐MI7, ACE 2‐MI7 and ACE 3‐MI7 compared to non‐infarcted and was lower in the ACE group 3‐MI7 than in the ACE groups 2‐MI7 and ACE 1‐MI7 (ACE 3‐MI7: 21,30 ± 1,47 vs. ACE 1‐MI7: 30,10 ± 1,80 and ACE 2‐MI7: 31,12 ± 1,47%). Regarding the autonomic parameters sympathetic modulation was higher in the ACE group 3‐MI7 than in the ACE 1, ACE 2 and ACE 1‐MI7 groups (ACE 3‐MI7: 14.85 ± 2.36 vs. ACE 1: 4.76 ± 2.00, ACE 2: 4.34 ± 1.40 and ACE 1‐MI7: 5.13 ± 1.88 ms2); and the sympatovagal balance was higher in the ACE group 3‐MI7 than in the ACE group 1‐MI7 (ACE 3‐MI7: 2.22 ± 0.17 vs. ACE 1‐MI7: 0.81 ± 0.25). When comparing infarcted groups 7 and 28 days after AMI, it was observed that the baroreflex efficiency index was higher in the ACE group 1‐MI28 than in the infarcted groups assessed 7 days after the infarction (ACE 1‐MI28: 0.28 ± 0.03 vs. ACE 1‐MI7: 0.15 ± 0.02, ACE 2‐MI7: 0.17 ± 0.01 and ACE 3‐MI7: 0.17 ± 0.01). Infarcted animals with 3 copies of the ACE gene had lower survival (41%) and animals with 1 copy of the ACE gene had greater survival (71%) at the end of the study.CONCLUSIONOur results of cardiac function, cardiovascular autonomic function and survival curve indicate that animals with three copies of the ACE gene presented a worse evolution after myocardial infarction in relation to the animals with one copy of the ACE gene.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Herbal Compounds with Special Reference to Gastrodin as Potential Therapeutic Agents for Microglia Mediated Neuroinflammation.

Activated microglia play a pivotal role neurodegenerative diseases by producing a variety of proinflammatory mediators including tumor necrosis factor-alpha (TNF-α), interleukin- 1beta (IL-1β) and nitric oxide (NO) that are toxic to neurons and oligodendrocytes. In view of the above, suppression of microglia mediated neuroinflammation is deemed a therapeutic strategy for neurodegenerative diseases. Several potential Chinese herbal extracts have been reported to exert neuroprotective effects against neurodegenerative diseases targeting specifically at the activated microglia. In this connection, the phenolic glucoside gastrodin, a main constituent of the Chinese herbal medicine Gastrodia rhizoma, produced widely in the local community exhibits potential neuroprotective effects through suppression of neurotoxic proinflammatory mediators. Here, we first review the roles of activated microglia in different brain diseases. The effects of gastrodin on activated microglia are then considered. We have identified gastrodin as a putative therapeutic agent as it has been found to suppress microglial activation thus ameliorating neuroinflammation. More importantly, gastrodin downregulates the expression of renin angiotensin system (RAS) and production of proinflammatory mediators. Remarkably, gastrodin promotes Sirtuin 3 (Sirt3) up-regulation and nicotinamide adenine dinucleotide phosphate oxidase-2 (NOX-2) down-regulation after ischemichypoxia in activated microglia mediated by AT1 or AT2 receptors which are angiotensin II receptors subtypes, indicating a possible molecular link between RAS and Sirt3 survival genes. This review summarizes the beneficial effects of gastrodin acting on activated microglia along with other herbal compounds. Its efficacy in neuroprotection is consistent with some common herbal products in China.

Wnt/β-catenin regulates blood pressure and kidney injury in rats

Activation of the renin-angiotensin system (RAS) plays a pivotal role in mediating hypertension, chronic kidney and cardiovascular diseases. As Wnt/β-catenin regulates multiple RAS genes, we speculated that this developmental signaling pathway might also participate in blood pressure (BP) regulation. To test this, we utilized two rat models of experimental hypertension: chronic angiotensin II infusion and remnant kidney after 5/6 nephrectomy. Inhibition of Wnt/β-catenin by ICG-001 blunted angiotensin II-induced hypertension. Interestingly, angiotensin II was able to induce the expression of multiple Wnt genes in vivo and in vitro, thereby creating a vicious cycle between Wnt/β-catenin and RAS activation. In the remnant kidney model, renal β-catenin was upregulated, and delayed administration of ICG-001 also blunted BP elevation and abolished the induction of angiotensinogen, renin, angiotensin-converting enzyme and angiotensin II type 1 receptor. ICG-001 also reduced albuminuria, serum creatinine and blood urea nitrogen, and inhibited renal expression of fibronectin, collagen I and plasminogen activator inhibitor-1, and suppressed the infiltration of CD3+ T cells and CD68+ monocytes/macrophages. In vitro, incubation with losartan prevented Wnt/β-catenin-mediated fibronectin, α-smooth muscle actin and Snail1 expression, suggesting that the fibrogenic action of Wnt/β-catenin is dependent on RAS activation. Taken together, these results suggest an intrinsic linkage of Wnt/β-catenin signaling with BP regulation. Our studies also demonstrate that hyperactive Wnt/β-catenin can drive hypertension and kidney damage via RAS activation.

Polymorphism of the renin-angiotensin system genes and endothelial NO-synthase gene in obese patients with arterial hypertension

Polymorphism of the renin-angiotensin system genes and endothelial NO-synthase gene in obese patients with arterial hypertension

Investigation of the correlation of allele polymorphism of renin-angiotensin system genes, nitric oxide synthase and folate cycle with the severity of ischemic stroke

Aim. To study the frequency of polymorphic gene variants encoding proteins of renin-angiotensin system [AGT Thr174Met (rs 4762), AGT Met235Thr (rs699), AGTR1 A1166C (rs5186)], endothelial factors [NOS3 C786T (rs2070744)], and folate cycle enzymes [MTHFR C677T (rs1801133)] in patients with various ischemic stroke severity. Methods. 98 patients with ischemic stroke verified by magnetic resonance imaging and computed tomography scan of the brain, were examined. The severity of stroke was assessed by National Institutes of Health Stroke Scale. The allelic variants of genes were typified by polymerase chain reaction with the detection of amplification products in the «real time» mode. Results. The analysis of genetic polymorphism frequency of renin-angiotensin system did not reveal statistically significant differences in the study groups. The polymorphism of NOSC786T gene in the study was also not associated with the severity of ischemic stroke. Among the studied polymorphic variants, only the C677T polymorphism of MTHFR gene was revealed to be reliably associated with severe course of acute cerebral ischemia. Conclusion. C677T polymorphism of MTHFR gene is reliably associated with severe course of acute cerebral ischemia; carriage of 677T allele of MTHFR gene in the studied category of patients can cause an increased level of homocysteine and have an adverse effect on the course of acute cerebral ischemia.

Association of renin-angiotensin system genes polymorphisms and risk of premature ST elevation myocardial infarction in young Mexican population.

: The renin-angiotensin system plays an important role in the regulation of blood pressure and the development of coronary artery disease. The aim was to examine the association of the insertion deletion in the angiotensin-converting enzyme gene, M235T and T174M polymorphisms in the angiotensinogen gene with ST elevation acute myocardial infarction (STEAMI) in young Mexican population. We analyzed 242 unrelated patients with STEAMI 45 or less years of age, admitted to a cardiovascular intense care unit, and 242 individuals without STEAMI matched by age and sex, recruited from January 2006 and June 2013. The polymorphisms insertion deletion, M235T and T174M were determined in all participants by a polymerase chain-reaction-restriction fragment length polymorphism assay. There was a significant difference in the insertion deletion genotype distribution between two groups (P = 0.03) and a higher percentage of the T allele M235T polymorphism in the group of STEAMI patients (P = 0.02). The T174M polymorphism was not associated (P = 0.08). The insertion deletion and M235T polymorphisms, smoking, hypertension, familial history of cardiovascular disease and dyslipidemia were independent risk factors for STEAMI. Our results identified that the D allele from the insertion deletion and M235T but not T174M polymorphisms represent an independent risk factor for STEAMI in young Mexican population.